rs201518979

Variant names:

• chr4-76710238-C-G
• rs201518979
• NM_020859.4:c.406C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-76710238-C-G
• chr4-76710238-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020859.4(SHROOM3):​c.406C>G​(p.His136Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H136Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

SHROOM3-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1584397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.406C>G	p.His136Asp	missense_variant	Exon 3 of 11	ENST00000296043.7	NP_065910.3
SHROOM3-AS1	NR_187404.1	n.1201G>C		non_coding_transcript_exon_variant	Exon 4 of 4
SHROOM3-AS1	NR_187405.1	n.657G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.406C>G	p.His136Asp	missense_variant	Exon 3 of 11	1	NM_020859.4	ENSP00000296043.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.027
Sift	Benign	0.039	D;.
Sift4G	Benign	0.33	T;.
Polyphen		0.44	B;.
Vest4		0.36
MutPred		0.30		Gain of ubiquitination at K138 (P = 0.0316);.;
MVP		0.23
MPC		0.51
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201518979; hg19: chr4-77631391;